Figure 3.
HMGB1 Blockade Does Not Affect oHSV Replication in GBM In Vitro and In Vivo
(A) GBM cell line (U87ΔEGFR) and patient-derived primary GBM cells (GBM 12 and GBM1016) were infected with HSVQ (MOI = 0.5) for 1 hr and treated with anti-HMGB1 antibody or isotype IgY (10 μg/mL) for 48 hr. Percentage of GFP-positive virus-infected cells was analyzed by flow cytometry analysis. (B–D) Nude mice (n = 6/group) bearing intracranial U87ΔEGFR glioma cells were treated with 5 × 105 pfu of luciferase-expressing oHSV (HSVQ-Luc) by direct intratumoral injection 8 days post-tumor-implant. Mice were randomized to receive isotype or anti-HMGB1 (100 μg/mouse) blocking antibodies by i.p. injection for 3 days (−1, 0, 1 dpi of oHSV). (B) Kaplan-Meier survival curves of intracranial glioma-bearing mice treated with HSVQ-Luc with and without anti-HMGB1-blocking antibody treatment (*p < 0.05 for oHSV + anti-HMGB1 versus oHSV + IgY). n = 6/group. (C and D) Virus replication was monitored by IVIS imaging. (C) Representative images of mice showing virus-encoded luciferase activity over time. (D) Data shown are changes in relative luciferase activity in individual mice after treatment with HSVQ-Luc with isotype (left) or HMGB1-blocking antibody (right).